Department of Ophthalmology, Visual and Anatomical Sciences, 12267Wayne State University School of Medicine, Detroit, Michigan, United States.
ASN Neuro. 2021 Jan-Dec;13:17590914211009851. doi: 10.1177/17590914211009851.
A founder mutation in human () was recently linked to a genetic leukoencephalopathy in Ashkenazi Jews that presents with the classical features of white matter disorders of the central nervous system (CNS). The neurological deficits include hypomyelination, hypotonia, gradual loss of vision, and seizures. However, the cells expressing the mutation were not identified. Here we describe, using immunocytochemistry, the strong expression of Vps11 in mouse oligodendrocytes and, specifically, its localization with Myelin Associated Glycoprotein (MAG) in the inner tongue of myelin. In longitudinal sections of myelin, it forms a bead-like structure, alternating with Myelin Basic Protein (MBP). Immunofluorescent staining with Vps11 and neurofilament proteins indicates the absence of Vps11 in axons . Finally, changes in Vps11 expression are associated with altered proteolipid protein (PLP) levels based upon mice with duplications or deletions of the gene. To determine potential functional contributions of Vps11, we combined Vps11 with Platelet Derived Growth Factor Receptor-α (PDGFRα) and : in both conditions, co-localization of the two proteins was frequently found in round vesicles of OPCs/oligodendrocytes, suggesting retrograde transport for degradation by the endolysosomal system. Neuron-to-glial communication has been invoked to explain degenerative changes in myelin followed by degenerative changes in axons, and vice versa; but to our knowledge, no specific proteins in retrograde transport from the myelin inner tongue to oligodendrocyte perikarya have been identified. The identification of mutations in and its localization at the axon-myelin interface should open new avenues of research.
人类 () 的一个起始突变最近与阿什肯纳兹犹太人中的一种遗传性脑白质病相关联，该疾病表现出中枢神经系统（CNS）白质疾病的典型特征。神经功能缺损包括少突胶质细胞发育不全、张力减退、视力逐渐丧失和癫痫发作。然而，表达该突变的细胞尚未被鉴定。在这里，我们使用免疫细胞化学描述了 Vps11 在小鼠少突胶质细胞中的强烈表达，特别是其与髓鞘相关糖蛋白（MAG）在髓鞘内舌部的定位。在髓鞘的纵切片中，它形成珠状结构，与髓鞘碱性蛋白（MBP）交替。Vps11 和神经丝蛋白的免疫荧光染色表明 Vps11 不存在于轴突中。最后，Vps11 表达的变化与根据基因的重复或缺失而改变的蛋白脂蛋白（PLP）水平相关。为了确定 Vps11 的潜在功能贡献，我们将 Vps11 与血小板衍生生长因子受体-α（PDGFRα）结合：在这两种情况下，两种蛋白质的共定位经常在 OPC/少突胶质细胞的圆形小泡中发现，表明通过内溶酶体系统进行逆行运输以进行降解。神经胶质细胞通讯已被提出用于解释髓鞘的退行性变化，随后是轴突的退行性变化，反之亦然；但是据我们所知，尚未鉴定出从髓鞘内舌部到少突胶质细胞胞体的逆行运输中的特定蛋白质。在轴突-髓鞘界面鉴定出的突变及其定位应该为研究开辟新的途径。
